T-ALL Breakthrough: CD5 CAR-T Shows Promise, Faces Challenges

Researchers at Peking University People's Hospital presented Phase I CONQUER trial results for a novel CD5 CAR-T therapy, SL105, targeting T-cell acute lymphoblastic leukaemia (T-ALL) and lymphoma. This therapy utilizes nanobodies to block CD5, preventing self-elimination of therapeutic cells. The trial involved 22 adult patients with refractory/relapsed disease.

The SL105 therapy demonstrated a three-month maximum objective response rate of 81.8%, with 54.5% achieving complete response. CAR-T expansion was observed, with persistence up to six months in one patient. However, the treatment was associated with significant safety concerns, including a 90.9% incidence of Grade 3 or higher infections, notably EBV and CMV.

Infection-related deaths occurred in seven patients who had not undergone stem cell transplantation. The median overall survival was 3.6 months. These findings highlight the therapy's potential but underscore the need for modifications to mitigate infectious risks and improve long-term outcomes, possibly by integrating earlier HCT.

This trial follows interim results from March Biosciences' MB-105, another CD5 CAR-T therapy, which also showed positive short-term efficacy. While these CAR-T therapies show promise as bridges to HCT, further research is needed to establish them as independent treatments with acceptable safety profiles.